全文获取类型
收费全文 | 594篇 |
免费 | 31篇 |
专业分类
625篇 |
出版年
2023年 | 4篇 |
2022年 | 6篇 |
2021年 | 14篇 |
2020年 | 8篇 |
2019年 | 14篇 |
2018年 | 16篇 |
2017年 | 13篇 |
2016年 | 17篇 |
2015年 | 27篇 |
2014年 | 28篇 |
2013年 | 32篇 |
2012年 | 53篇 |
2011年 | 44篇 |
2010年 | 33篇 |
2009年 | 26篇 |
2008年 | 25篇 |
2007年 | 29篇 |
2006年 | 35篇 |
2005年 | 15篇 |
2004年 | 21篇 |
2003年 | 15篇 |
2002年 | 9篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1998年 | 7篇 |
1997年 | 19篇 |
1996年 | 7篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 5篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1966年 | 2篇 |
1965年 | 3篇 |
1910年 | 2篇 |
排序方式: 共有625条查询结果,搜索用时 15 毫秒
111.
During an initial study in searching for the alternative derivatives suitable for photolabeling of neuroactive steroids, perfluorobenzoates and perfluorobenzamides in position 17 of 5β-androstan-3α-ol were synthesized from the corresponding 17-hydroxy and 17-amino derivatives. After transformation into glutamates or sulfates, 17α-epimers had comparable inhibitory activity at NMDA receptors to the natural neurosteroid (20-oxo-5β-pregnan-3β-yl sulfate), however, were more potent (2- to 36-fold) than their 17β-substituted analogs. In one case, fluorine in position 4' of perfluorobenzoate group was substituted with azide and activity of the final glutamate was retained comparing with the corresponding perfluorobenzoate. The series was expanded with perfluorobenzoyl derivatives of pregnanolone: Perfluorobenzamide of glutamate and perfluorobenzoate of 11α-hydroxy pregnanolone were prepared and tested. From nine tested compounds, four of them exhibit very good inhibition activity and can serve as promising leads for photolabeling experiments. 相似文献
112.
113.
114.
115.
Símová S Klíma M Cermak L Sourková V Andera L 《Apoptosis : an international journal on programmed cell death》2008,13(3):423-436
TRAIL, a ligand of the TNFα family, induces upon binding to its pro-death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5 the apoptosis
of cancer cells. Activated receptors incite the formation of the Death-Inducing Signaling Complex followed by the activation
of the downstream apoptotic signaling. TRAIL-induced apoptosis is regulated at multiple levels, one of them being the presence
and relative number of TRAIL pro- and anti-apoptotic receptors on the cytoplasmic membrane. In a yeast two-hybrid search for
proteins that interact with the intracellular part (ICP) of DR4, we picked ARAP1, an adapter protein with ArfGAP and RhoGAP
activities. In yeast, DR4(ICP) interacts with the alternatively spliced ARAP1 lacking 11 amino acids from the PH5 domain.
Transfected ARAP1 co-precipitates with DR4 and co-localizes with it in the endoplasmic reticulum/Golgi, at the cytoplasmic
membrane and in early endosomes of TRAIL-treated cells. ARAP1 knockdown significantly compromises the localization of DR4
at the cell surface of several tumor cell lines and slows down their TRAIL-induced death. ARAP1 overexpressed in HEL cells
does not affect their TRAIL-induced apoptosis or the membrane localization of DR4, but it enhances the cell-surface presentation
of phosphatidyl serine. Our data indicate that ARAP1 is likely involved in the regulation of the cell-specific trafficking
of DR4 and might thus affect the efficacy of TRAIL-induced apoptosis.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
116.
Ladislav Tamás Katarína Ďurčeková Jana Huttová Igor Mistrík 《Acta Physiologiae Plantarum》2009,31(1):139-144
The expression of defence-related peroxidases Prx7 and Prx8 in barley roots grown under selected abiotic stress conditions
(toxic metals: Cd, Al, Co, Cu, Hg; drought, salinity, extreme temperatures: heat, cold) and compounds activating (2,4-D) or
inhibiting (SHAM) POD activity as well as H2O2 and H2O2 scavenger (DTT) was characterized. Strong Cd concentration dependent expression of Prx8 peroxidase gene was observed, which
correlated with root growth inhibition induced by Cd- and some other stress factors (heavy metals, heat and salinity). Application
of H2O2 did not cause changes in expression of Prx8, but H2O2 scavenger (DTT) as well as the inhibitor (SHAM) and the activator (2,4-D) of PODs induced increase in Prx8 expression. Our
results demonstrate that root growth inhibition during any disturbance of active oxygen species (AOS) in root tissue is correlated
with up-regulation of Prx8 gene expression in barley roots. 相似文献
117.
Sodium methoxide-promoted methanolysis of 7-deoxy-7-nitro-L-glycero-L-galacto-heptitol peracetate rapidly and nearly quantitatively accumulates 7-deoxy-6-O-methyl-7-nitro-L-glycero-L-galacto-heptitol. The prolonged treatment then provides 76% of D-galactofuranosyl nitromethanes and finally results in the equilibrium of 77% of β-D-galactopyranosyl nitromethane and 7-9% of three other tautomeric D-galactosyl nitromethanes. Thermal treatment of 7-deoxy-7-nitro-L-glycero-L-galacto-heptitol in boiling water peaks at a 58% content of D-galactofuranosyl nitromethanes and ends in a similar equilibrium mixture of four D-galactosyl tautomers. The relevant kinetic parameters of the latter transformation are determined by a curve fitting using the nonlinear least-squares Marquardt-Levenberg algorithm. 相似文献
118.
Many techniques have been applied to understand viral cell-to-cell movement in host plants, but little progress has been made in understanding viral vascular transport mechanisms. We propose the use of chlorophyll fluorescence imaging techniques, not only to diagnose the viral infection, but also to follow the movement of the virus through the vascular system and its subsequent spread into the leaves. In Nicotiana benthamiana plants, imaging of chlorophyll fluorescence parameters such as ФPSII and NPQ proved useful to follow infections with Pepper mild mottle virus. The results demonstrate a correlation between changes in the chlorophyll fluorescence parameters and the viral distribution analyzed by tissue printing. 相似文献
119.
120.
Carlos Angel Espinosa-Vinals Jiri Masin Jana Holubova Ondrej Stanek David Jurnecka Radim Osicka Peter Sebo Ladislav Bumba 《The Journal of biological chemistry》2021,297(1)
The whooping cough agent Bordetella pertussis secretes an adenylate cyclase toxin (CyaA) that through its large carboxy-proximal Repeat-in-ToXin (RTX) domain binds the complement receptor 3 (CR3). The RTX domain consists of five blocks (I–V) of characteristic glycine and aspartate-rich nonapeptides that fold into five Ca2+-loaded parallel β-rolls. Previous work indicated that the CR3-binding structure comprises the interface of β-rolls II and III. To test if further portions of the RTX domain contribute to CR3 binding, we generated a construct with the RTX block II/III interface (CyaA residues 1132–1294) linked directly to the C-terminal block V fragment bearing the folding scaffold (CyaA residues 1562–1681). Despite deletion of 267 internal residues of the RTX domain, the Ca2+-driven folding of the hybrid block III/V β-roll still supported formation of the CR3-binding structure at the interface of β-rolls II and III. Moreover, upon stabilization by N- and C-terminal flanking segments, the block III/V hybrid-comprising constructs competed with CyaA for CR3 binding and induced formation of CyaA toxin-neutralizing antibodies in mice. Finally, a truncated CyaAΔ1295-1561 toxin bound and penetrated erythrocytes and CR3-expressing cells, showing that the deleted portions of RTX blocks III, IV, and V (residues 1295–1561) were dispensable for CR3 binding and for toxin translocation across the target cell membrane. This suggests that almost a half of the RTX domain of CyaA is not involved in target cell interaction and rather serves the purpose of toxin secretion. 相似文献